This is a Phase II multi-institutional study for patients with histological diagnosis of colo-rectal cancer, with p185 HER2 overexpression (2+ or 3+ using DKO IHC system). Patients must have at least one bidimensionally measurable indicator lesion that has not been irradiated. Measurable lesions must have the following minimum dimensions: A skin nodule or superficial lymph node 2 cm x 2 cm or a lung lesion surrounded by aerated lung 1 cm x 1 cm if by chest x-ray; at lest 2 cm in one dimension if by CT scan. Patients will be treated with Trastuzumab 4/mg/kg loading dose on week 1, followed by 2 mg/kg q weekly CPT-11, 125 mg/m2 q weekly x 4 with a two week rest period (one cycle). Staging evaluation after every two cycles of CPT-11. Patients with stable or responding disease will continue treatment. Assess LVEF by ECHO/MUGA scans after every two cycles of CPT-11.